Anti-PMP22 antibodies in patients with inflammatory neuropathy

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Abstract

An experimental model of inflammatory radiculoneuropathy is induced by immunising rats with peripheral myelin protein 22 (PMP22). We have investigated whether PMP22 may be important in inducing human inflammatory neuropathy. We examined sera of patients with Guillain–Barré syndrome (GBS), chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), other neuropathies (ONP) and normal controls for IgM and IgG antibodies against PMP22 by ELISA (against synthetic PMP22 extracellular peptide fragments) and Western blot (against cauda equina). Antibodies were detected by both methods in 52% of patients with GBS, 35% with CIDP, 3% with ONP and no normal controls. We conclude that an immune response against PMP22 may play a role in the pathogenesis of the inflammatory neuropathies.

Introduction

The response of inflammatory demyelinating neuropathies to plasma exchange suggests a role for circulating antibodies in the pathogenesis of these disorders. Antibodies to the myelin proteins P2, P0 and myelin-associated glycoprotein (MAG) (Koski et al., 1986, Sato et al., 1986, Quarles et al., 1990, Khalili-Shirazi et al., 1993, Ellie et al., 1996, Melendez-Vasquez et al., 1997) and to a variety of gangliosides especially GM1 and GQ1b (Gregson et al., 1991, Willison and Veitch, 1994, Oomes et al., 1995, Rees et al., 1995, Ho et al., 1997, Jacobs et al., 1997, Pestronk and Choksi, 1997, Yuki, 1998) have been detected in patients with acute and chronic demyelinating neuropathies. Antibodies to GD1a have been detected in patients with acute motor axonal neuropathy (Ho et al., 1999). With the probable exceptions of ganglioside GQ1b in Miller Fisher syndrome (Willison and Veitch, 1994), ganglioside GD1a in acute motor axonal neuropathy (Ho et al., 1999) and ganglioside GM1 in multifocal motor neuropathy (Pestronk and Choksi, 1997) no specific characteristic autoimmune target has been detected in these disorders and whether any of these antibodies are implicated in the pathological process or are merely phenomena following demyelination is still debated.

We have previously shown that recombinant, homologous peripheral myelin protein 22 (PMP22) induces experimental autoimmune neuritis (EAN) in the Lewis rat, an experimental model of acute inflammatory demyelinating polyradiculoneuropathy, the most common form of GBS (Gabriel et al., 1998). The animals in this model developed antibodies against the immunising antigen. Since PMP22 is expressed on the extracellular surface of the myelin membrane (i.e., at the intraperiod line), antibodies against it might induce demyelination and so play a part in the pathogenesis of autoimmunity. It was therefore of interest to determine whether antibodies to PMP22 are generated in human inflammatory neuropathies.

Section snippets

Patients

Sera from 19 patients with GBS, 17 with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), 30 with other neuropathies (ONP) and 51 normal control sera were collected between January 1993 and June 1997 and stored at −70°C. Patients with GBS fulfilled the diagnostic criteria of Asbury and Cornblath (1990). They were classified as having acute inflammatory demyelinating polyradiculoneuropathy (AIDP) or acute motor axonal neuropathy (AMAN) according to the criteria of Hadden et al.

Patient demographics

Characteristics of the subjects in each group are shown in Table 1 and individual features of the patients with GBS in Table 2.

The normal subjects were significantly younger than the ONP group (P<0.05) but there were no other differences between the ages of the groups. The proportion of men in the GBS and CIDP groups was higher than in the ONP group or in normal controls. Serum was taken acutely, before treatment, in 18 out of 19 patients with GBS and 2 days following the first plasma exchange

Discussion

Although there have been many investigations of antibodies to different myelin constituents in GBS and related disorders this is the first report of antibodies to human PMP22.

In this study we had access to a retrospective library of sera from well documented patients collected for other purposes. We intend to extend our investigation to include serial samples from a larger panel of sera from patients collected prospectively to allow analysis of possible correlations between the type, stage,

Acknowledgements

C.M.G. was supported by a research fellowship from the British Brain and Spine Foundation. We thank Dr. Steve Moore for his expert help in synthesising the PMP22 peptides.

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